High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

Abstract

dWe conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TSTpositive (induration, >10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P ‫؍‬ 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for >12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy.

Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases

“…The rate of conversion ranged from 0% to 37% for the TST,15–20 from 4% to 12% for QFT-G,14 17 from 0% to 12% for QFT-GIT18–20 22 and from 0% to 10.5% for T-SPOT.TB21 (duration of follow-up: 3 months to >3 years). In general, the rate of conversion was higher in high TB prevalence countries.…”

Tuberculosis screening in patients receiving biological therapy

“…2 patients had multiple sclerosis, other 2 had psoriasis and 1 had Crohn' s disease. They were treated with natalizumab (2), infliximab (2) and etanercept (1). New TB exposure since the baseline screening was not reported.…”

“…The advent of biological therapies has greatly improved the treatment and management of immunomediated diseases such as Crohn' s disease, psoriasis, rheumatoid arthritis, ankylosing spondylitis and multiple sclerosis [1][2][3] , allowing for a better quality of life for these patients 4 . Biologic drugs are now a staple in the clinical appro ach to severe forms of these diseases.…”

Opportunistic infections in patients with idiopathic inflammatory myopathies

“…The cumulative and mean daily doses of steroids during the first year of rheumatic disease and over follow up, together with a history of pulse therapy, increase the probability of developing tuberculosis (TB) by up to five‐fold the risk in the general population . The association of TB with biologic therapy is well‐recognized, and several guidelines provide recommendations to reduce the risk of this infection . In patients with rheumatic diseases, international recommendations for managing latent TB infection are well established with regard to biological therapies, but they are not so clear about other immunosuppressive therapies, including glucocorticoids.…”

“…25 The association of TB with biologic therapy is well-recognized, and several guidelines provide recommendations to reduce the risk of this infection. 26 In patients with rheumatic diseases, international recommendations for managing latent TB infection are well established with regard to biological therapies, 27 but they are not so clear about other immunosuppressive therapies, including glucocorticoids. As a general rule, latent TB is sought when more aggressive immunosuppressive therapy is started and/or when prednisone doses higher than 15 mg/day are administered in older persons for at least 1 month.…”